Bacterial infections are a major health problem and pose a large economic burden on our society. Bacterial infections can be caused by a wide range of bacteria, resulting in mild to life-threatening illnesses that require immediate intervention. Common bacterial infections include for example pneumonia, ear infections, diarrhea, urinary tract infections, and skin disorders.
For example, Streptococcus pneumoniae (pneumococcus) causes respiratory tract infections among infants and the elderly worldwide. Capsular polysaccharide is the main virulence factor, and its composition defines 91 serotypes of pneumococcus. Certain serotypes colonize asymptomatically the human nasopharynx representing a reservoir for inter-individual transmission of the bacteria. In some individuals colonization may progress to pneumococcal pneumonia and invasive disease. Other examples include Salmonella enterica which cause significant morbidity and mortality worldwide. The predominant Salmonella enterica serovars causing disease in humans are Typhi, Paratyphi A and B, and Typhimurium. The Typhi and Paratyphi serovars are strict human pathogens and cause typhoid fever, while the non-typhoidal Salmonella enterica subspecies Typhimurium results primarily in gastroenteritis in humans.
The treatment of bacterial infections is most often achieved by using antibiotics which either aim at killing invading bacteria (bactericide mode of action) or inhibiting their growth (bacteriostatic mode of action) without harming the host. Antibiotic effectiveness depends on mechanism of action, drug distribution, site of infection, immune status of the host, and resistance factors of bacteria. Antibiotics work through several mechanisms; some inhibit the formation of bacterial cell walls. Others interrupt bacterial protein synthesis. Yet some others inhibit metabolism or interfere with DNA synthesis and/or cell membrane permeability.
It is however becoming more evident, that antibiotics do not always perform to the extent they should. Some infections cannot be cleared, even if the pathogen is sensitive to the used antibiotic. This inability to completely kill all bacteria poses a severe problem once the antibiotic treatment is stopped, as the infection relapses and the patients fall ill anew. Moreover, the constant antibiotic pressure and the natural competence of some strains results in frequent resistance to antibiotics. The increasing burden of antimicrobial resistance coupled with the decreasing number of antibiotics in development has urged for strategies to maximize the therapeutic index of existing antibiotics.